Fabrication Of Two-dimensional MXenes Composite Nanomaterials And Their Photothermal-photodynamic Bifunctional Diagnosis And Treatment

MXenes have attracted the increasing attention as one of oncotherapy materials,thanks to its two dimentional/stable skeleton structure,active surface loading properties,high specific surface area and so on.Since possessing the advantage of high pore capacity,easy surface modification and good biocompatibility,mesoporous Silicon Oxide（mSiO₂）has great application potential on protective and carrier materials.Taking MXenes as the carrier,the anti-tumor drugs are modified by MnO_x,mSiO₂,photosensitizer and active target agent.Combined with the method of multi-photo therapy,the system can improve the efficiency of tumor treatment more effectively.In this work,we report on the rational construction of a composite multifunctional nanosystems with multiple photonic response for achieving concurrent photodynamic therapy and photothermal hyperthermia with simultaneous active-targeting,tumor microenvironment-sensitive and synergistic functionality and efficacy.Firslyt MXenes Nb₂C nanosheets were successfully prepared by two-step liquid phase stripping method,and MnO_x was preloaded onto Nb₂C and coated with mSiO₂.MnO_x/Nb₂C@mSiO₂ nanosheet was modified by surface modification engineering to keep it stable in physiological solution.At the same time,active-targeting polypeptide complexation enabled MnO_x/Nb₂C@mSiO₂-RGD nanosheets enriched in tumor cells,thus improving the therapeutic effect of the drug.Mesoporous structure can meet the potential of other drug loads,and Ce6,as a good photosensitizer,makes the whole system provide a good foundation for the successful implementation of PDT&PTT coordinated treatment.Secondly,according to lambert’s law,the extinction coefficient of Ce6/MnO_x/Nb₂C@mSiO₂-RGD composite nanosheet was calculated to be 31.68 L g^-1cm^-1.The photothermal conversion efficiency was calculated to be 26.21%,for the report of Roper et al.Heating curves showed that solution temperature become 58℃in 8 minutes at 50μg mL^-1.It shows that the composite nanosheet can efficiently and rapidly convert NIR-II light into thermal energy.The O₂ content in the solution was detected by the O₂ microsensor,which could alleviate the problem of hypoxia in the tumor microenvironment and enhance the photodynamic effect.The generation of ¹O₂was measured by uv-vis absorption spectra,indicating the good photodynamic effect of Ce6/MnO_x/Nb₂C@mSiO₂-RGD composite nanosheet.Thirdly,the synergistic effect of in vitro PDT&PTT on Ce6/MnO_x/Nb₂C@mSiO₂-RGD composite nanosheets were verified by in vitro cell experiments.In vitro cytotoxicity experiments showed that the appropriate concentration of Ce6/MnO_x/Nb₂C@mSiO₂-RGD composite nanosheets had no significant toxicity to U87 cells.Ce6/MnO_x/Nb₂C@mSiO₂-RGD composite nanosheets actively targeted to U87 tumor cells and enriched in the cells.As a result,Ce6/MnO_x/Nb₂C@mSiO₂-RGD composite nano-sheet can meet the requirement of PDT&PTT synergistic killing tumor cells at a very low concentration.Finally,glioma transplantation model of mouse in vivo was established,then blood and tissue sections of mice injected with drugs were analyzed to confirm that appropriate amount of composite nanosheets had no obvious damage to mice.RGD targeted at U87 glioma on the surface of composite nanosheet,and Ce6/MnO_x/Nb₂C@mSiO₂-RGD content was enriched in tumor cells of mice.After different treatments,the killing effect of mutil-photon treatment system on tumor tissue had no residual tumor and no recurrence which is obviously better than that of single light treatment.At the end of therapy,tumor mass also showed an ideal targeted and synergistically enhanced PDT&PTT in the treatment of glioma.